Autoimmune neurologic disease testing is complex, and essential for diagnosis

When a neurologic autoimmune disorder is suspected, testing is essential to confirm the diagnosis. The testing regimen is complex, but when done right, it provides maximum insights into what antibodies a patient has and how they are causing symptoms.

In most cases, autoimmunity is due to production of autoantibodies against 1 or more of the body’s own tissues, with neurologic autoantibodies targeting various components of the peripheral and central nervous system. This ranges from well-known disorders like multiple sclerosis to rare conditions such as autoimmune encephalitis. The diverse spectrum of neurologic autoimmune diseases underscores the importance of precise diagnosis, as symptoms often overlap and treatment strategies vary, necessitating tailored approaches for optimal care.

The spectrum of neurologic autoimmune diseases

Treatments for each disease differ greatly, making the correct diagnosis essential to timely and effective care.

In autoimmune encephalitis, autoantibodies account for many cases. Some forms of this condition (called paraneoplastic syndromes) are associated with an underlying tumor; an immune system attack against the tumor produces antibodies that may target certain intracellular proteins as well. In other forms, there is no tumor, and antibodies may form for unknown reasons against proteins on the neuron’s surface.

Alternatively, the most common cause of myasthenia gravis, and the one discovered earliest, is production of antibodies against the acetylcholine receptor on the surface of skeletal muscle. Two other causes include antibodies against MuSK and LRP4, which form a complex that promotes activity of the acetylcholine receptor. Other targets for autoantibodies include the ryanodine receptor and the intracellular protein titin.

Demyelinating disorders, including multiple sclerosis, neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein (MOG) antibody disease, are characterized by distinct autoantibodies targeting specific cellular components, highlighting the need for precise diagnostic methodologies.

Other neurologic autoimmune diseases include some forms of peripheral neuropathy as well as rarer conditions. Given the pace of autoantibody discovery in recent years, it is highly likely that more causes of these diseases have yet to be discovered.

The importance of antibody testing

Antibody testing is complex and often may include both in vitro and tissue-based testing. A tissue immunofluorescence assay (IFA) is often the first step when evaluating a patient suspected of having a neurological autoimmune disease. At Quest, our approach to IFA involves an antibody binding challenge using primate tissue. We then compare our findings with other primate tissues to differentiate antibodies, narrow down specific analytes, and conduct a detailed examination of various patterns. More than 1 tissue test may be involved, to narrow the range of possible autoantibodies involved.

 If warranted by the IFA, a Western line blot reflex test may be used as a confirmatory test. This method is used to confirm tissue IFA patterns by placing a specific protein on a membrane and measuring antibody binding semiquantitatively.

For definitive detection, central nervous system autoantibodies may require a cell-based assay (CBA). In this assay, the suspected antigen is recombinantly expressed in cells and then exposed to the patient sample containing the autoantibodies. Studies have shown the yield is much higher for this type of assay than for IFA alone. Radioimmunoassay (RIA) may then be used to quantify the levels of autoantibodies.

Improving diagnosis speed with a patient-focused approach

When a patient presents with a range of neurological symptoms, it can be difficult to identify what is causing them because clinical presentations do not always correlate with classic descriptions of autoantibody-associated diseases. In a study of 16,700 samples tested for neurological autoantibodies, approximately 50% tested positive for autoantibodies other than those included in the initial testing order. By screening for multiple autoantibodies, the detection rate for diagnostically relevant autoantibodies increased by 87% compared with testing for only the requested autoantibodies.¹

Unrivaled expertise for better outcomes

With over 650+ medical and scientific experts across Quest Diagnostics, our team can help make the differential diagnoses that are critical for appropriate treatment. Karthik Kuppusamy, PhD, senior vice president, Clinical Solutions at Quest Diagnostics, emphasizes the importance of timely testing in patient care. “For many patients, the road to a diagnosis is not linear and is quite challenging. Untangling the mysteries in neuroimmunology to help a patient overcome the obstacles in their diagnostic journey—so they get the right diagnosis and the right treatment—is what drives us.”